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. 2020 Aug 25;15(8):e0237302. doi: 10.1371/journal.pone.0237302

Chest CT findings related to mortality of patients with COVID-19: A retrospective case-series study

Yiqi Hu 1,#, Chenao Zhan 1,#, Chengyang Chen 2, Tao Ai 1,*, Liming Xia 1
Editor: Muhammad Adrish3
PMCID: PMC7447035  PMID: 32841294

Abstract

Background

As the current outbreak of COVID-2019 disease has spread to the other more than 150 countries besides China around the world and the death number constantly increased, the clinical data and radiological findings of death cases need to be explored so that more physicians, radiologists and researchers can gain important information to save more lives.

Methods

73 patients who died from COVID-19 were retrospectively included. The clinical and laboratory data of the patients were extracted from electronic medical records. The clinical data, inflammation-related laboratory results, and CT imaging features were summarized. The laboratory results and dynamic changes of imaging features and severity scores of lung involvement based on chest CT were analyzed.

Results

The mean age was 67±12 years. The typical clinical symptoms included fever (88%), cough (62%) and dyspnea (23%). 65% patients had at least one underlying disease. GGO with consolidation was the most common feature for the five lung lobes (47%-53% among the various lobes), with total severity score of 12.97±5.87 for the both lungs. The proportion of GGO with consolidation is markedly increased on follow-up chest CT compared with initial CT scans, as well as the averaging total CT scores (14.53±5.76 vs. 6.60±5.65; P<0.001). The severity score was rated as severe (white lung) in 13% patients on initial CT scans, and in 60% on follow-up CT scans. Moderate positive correlations were found between CT scores and leucocytes, neutrophils and IL-2R (r = 0.447–0581, P<0.001).

Conclusion

Chest CT findings and laboratory test results were worsening in patients who died of COVID-19, with moderate positive correlations between CT severity scores and inflammation-related factors of leucocytes, neutrophils, and IL-2R. Chest CT imaging may play an more important role in monitoring disease progression and predicting prognosis.

Introduction

In December 2019, an outbreak of new coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was initially reported in Wuhan City, China. The disease was then rapidly sweeping through the whole country and has spread to the other more than 150 countries and territories around the world. On March 13, 2020, the World Health Organization (WHO) declared the novel coronavirus outbreak to be a pandemic [1] and as of July 12, 2020, 7:15 GMT, accumulative 12,879,917 confirmed cases and 568,546 deaths were reported in countries.

The infection of SARS-CoV-2 shares highly homological features with SARS-CoV, and causes acute, lethal respiratory pneumonia with typical clinical symptoms of fever and cough. According to an earlier report by WHO, most patients (80%) experienced mild to moderate illness, and about 14% experienced severe disease and 5% were critically ill [2, 3].

The estimated mortality rate of COVID-19 is 3.5% on a global-wide scale, which is relatively low compared with the SARS-CoV and MERS-CoV [4]. However, it varies by location, the intensity of transmission, and infection prevention and control measures. The mortality reached up to 6% in Wuhan (early epicenter area) in the early stage of the outbreak, and current 12.7% in Italy due to the rapid increase in the number of infections and shortage of medical resources. What is more, the mortality in critically ill patients has been reported as high as 60% [5]. In this context, early identification of risk factors for poor prognosis, accurate evaluation of disease severity and monitoring disease progression will be essential to reduce the mortality rate of patients with COVID-19.

Chest CT imaging plays a valuable role in the screening and dynamic evaluation of patients with COVID-19 [6, 7]. Most patients with COVID-19 have typical CT imaging features of multiple ground-glass opacity (GGO) and/or consolidations in a peripheral distribution, which also reflects the severity of pulmonary inflammation. We assumed that chest CT features and dynamic changes may serve as an important biomarker for the risk stratification, prognostic prediction, and therapy decision of severe patients with COVID-19. To the best of our knowledge, no studies regarding chest CT characteristics related to the mortality of patients with COVID-19 have been reported until now.

In this study, we aimed to explore the chest CT imaging features of patients who died from COVID-19, correlating with essential clinical information and laboratory test results. We hope the results of this study will contribute to clinicians’ comprehension and treatment plan of COVID-19.

Materials and methods

Patients

This retrospective study was approved by the institutional review boards (IRB) of Tongji Hospital and written informed consent was waived due to the outbreak of COVID-19. 153 patients who highly likely died from COVID-19 from January 27 to February 28, 2020, were retrospectively reviewed in Tongji hospital (the largest general hospital designated for the treatment of severe patients with COVID-19 in Wuhan). The inclusion criteria based on the latest guideline of Diagnosis and Treatment of Pneumonitis caused by COVID-2019 [8] were: (1) positive real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) results with throat swab or lower respiratory tract samples; (2) available chest CT images; (3) available clinical and laboratory data. The exclusion criteria were: (1) the patient had chest CT images with very poor quality due to motion artifact; (2) the patient died of a severe underlying extra pulmonary disease. Finally, 73 patients were included in this study.

Clinical and laboratory data

The clinical and laboratory data of the patients were extracted from clinical electronic medical records in the hospital information system (HIS). The demographic information, clinical symptoms and signs, underlying chronic diseases were recorded for all patients. Laboratory results mainly included peripheral blood cell counts, inflammatory cytokines (interleukin-1β [IL-1β], interleukin-2 receptor [IL-2R], interleukin-6 [IL-6], interleukin-8 [IL-8], interleukin-10 [IL-10], and tumor necrosis factor α [TNF-α]), and infection-related biomarkers (procalcitonin [PCT], erythrocyte sedimentation rate [ESR], serum ferritin [SF], high sensitive C-reactive protein [hs-CRP]). The results of laboratory tests immediately after the hospital admission and before the death were selected for the comparison in this study.

Chest CT acquisition

All chest scans images were obtained with three CT systems (uCT 780, United Imaging, China; Optima 660, GE, America; Somatom Definition AS+, Siemens Healthineers, Germany). The patients were scanned in a supine position during breath-holding. The main imaging parameters were: tube voltage = 120 kVp, automatic tube current modulation (30–70 mAs), pitch = 0.99–1.22 mm, matrix = 512 × 512, slice thickness = 10 mm, field of view = 350 mm × 350 mm. All images were then reconstructed with a slice interval of 0.625 to 1.250 mm.

CT image analysis

All CT images were analyzed by two chest radiologists in consensus (Y.Q.H. and C.A.Z with 6 and 3 years of experience in interpreting chest CT images, respectively), who were blinded to clinical and laboratory data. The main features of CT images were described as the following four patterns: ground-glass opacity, ground-glass opacity with consolidation, consolidation and other (linear opacities, traction bronchiectasis, cysts, and reticular opacities) for each patient’s initial chest CT scan and last follow-ups if available. Each of the five lung lobes was visually scored for the degree of lung involvements using a 4-point- scale: 0, no involvement; 1, 1–25% involvement; 2, 26%-49% involvement; 3, 50%-75% involvement; 4, 76%-100% involvement [9]. The total severity CT score (the extent of pulmonary disease) was the sum of the five individual lobar scores and defined as follows: 0, none; 1–5, minimal; 6–10, mild; 11–15, moderate; and 16–20, severe involvement of the lung (white lung). The dynamic changes of imaging features and total severity scores were evaluated on the follow-up chest CT scans if available.

Statistical analysis

Statistical analysis was performed by using SPSS for Windows (version 20.0, SPSS Inc., Chicago, IL, USA). All quantitative variables were expressed as mean value ± standard deviation (SD) or median with range unless otherwise specified. All categorical variables were expressed as frequency with percentage. The differences in laboratory test results immediately after the hospital admission and before the death were compared by the paired-sample t-test. The difference in chest CT scores between the initial and follow-up CT scans, and among the different periods were compared by Wilcoxon rank-sum test and Mann-Whitney U test. The correlation between CT scores and inflammation-related parameters (selected from the time point closest to the examination time of chest CT scans) was calculated by Spearman correlation. The strength of the correlation (r) was defined as follows: │r│<0.20, very weak; 0.20≤│r│<0.40, weak; 0.40≤│r│<0.60, moderate; 0.60≤│r│<0.80, strong; 0.80≤│r│≤1.0, very strong. A P-value of less than 0.05 was considered statistically significant.

Results

General clinical and laboratory results

A total of 73 patients with confirmed COVID-19 were enrolled in this retrospective study. The mean age was 67±12 years with a range of 33–95 years. 65% patients had at least one underlying disease or condition (Table 1). 9% patients had chronic pulmonary diseases and 10% patients had a smoking history. The typical clinical symptoms included fever (88%), dry cough (62%) and dyspnea (23%). Besides, 10% patients experienced diarrhea during the disease course. 26% patients received intubation. 1% patients underwent a tracheotomy and 3% patients received extracorporeal membrane oxygenation (ECMO) therapy. For the laboratory tests (Table 2), leucocytes, neutrophils and neutrophil-to-lymphocyte ratio at the time before the death were significantly elevated than those at the time immediately after the admission (P<0.001, P = 0.004, 0.014, respectively). The levels of inflammatory cytokines of IL-6 and TNF-α and infection-related biomarker of SF were also significantly increased with the disease progression (P = 0.038, 0.048 and 0.022, respectively).

Table 1. Clinical characteristics of all patients.

Patient (n = 73)
Age (years)
Mean 67 ± 12
Range 33–95
≤40 1 (1%)
41–60 20 (27%)
61–80 41 (56%)
≥81 11 (15%)
Male 54 (74%)
Underlying disease or conditions 44/68 (65%)
Hypertension 29/68 (43%)
Diabetes 12/68 (18%)
Cardiovascular/Cerebrovascular disease 12/68 (18%)
Chronic kidney disease 7/68 (10%)
Malignancy 7/68 (10%)
Chronic pulmonary disease 6/68 (9%)
Administration of immunosuppressive agents 1/68 (1%)
Smoking history 7/73 (10%)
Initial CT scan to (median, days)
Onset of symptoms 8 (1–39)
Death 11 (1–36)
Follow up CT 5 (2–27)
Onset of symptoms to death (median, days) 19 (8–41)
Symptoms and signs
Fever 64/73 (88%)
Dry cough 45/73 (62%)
Expectoration 10/73 (14%)
Dyspnea 17/73 (23%)
Chest distress 16/73 (22%)
Fatigue 13/73 (18%)
Diarrhea 7/73 (10%)
Chills 2/73 (3%)
Myalgia 3/73 (4%)
Dizziness 2/73 (3%)
Coma 1/73 (1%)
None 1/73 (1%)
Intubation 19/73 (26%)
Tracheotomy 1/73 (1%)
ECMO 2/73 (3%)

Value listed as mean N (%), except annotated values.

Table 2. Laboratory test results of inflammation-related parameters.

After admission Before death P-value
Leucocytes (×109 per L) 9.88 ± 5.26 12.53 ± 7.41 <0.001
 Increased 33/71 (46%) 37/71 (52%)
Neutrophils (×109 per L) 8.68 ± 5.21 11.44 ± 12.07 0.003
 Increased 46/71 (65%) 51/71 (72%)
Lymphocytes (×109 per L) 0.71 ± 0.42 0.77 ± 1.40 0.739
 Decreased 60/71 (85%) 63/71 (89%)
Neutrophil-to-lymphocyte ratio 17.72 ± 15.66 27.14 ± 49.01 0.014
Interleukin-1β (pg/mL) 7.82 ± 12.72 7.72 ± 12.56 0.665
 Increased 7/45 (16%) 9/45 (20%)
Interleukin-2 receptor (U/mL) 1251.04 ± 791.74 1397.22 ± 903.77 0.109
 Increased 35/45 (78%) 35/45 (78%)
Interleukin-6 (pg/mL) 147.01 ± 315.60 425.45 ± 617.56 0.038
 Increased 44/45 (98%) 43/45 (96%)
Interleukin-8 (pg/mL) 50.85 ± 85.09 96.51 ± 246.52 0.179
 Increased 10/45 (22%) 14/45 (31%)
Interleukin-10 (pg/mL) 15.81 ± 18.12 17.95 ± 21.43 0.180
 Increased 25/45 (56%) 25/45 (56%)
Tumor necrosis factor α (pg/mL) 12.50 ± 6.96 15.85 ± 11.18 0.048
 Increased 32/45 (71%) 32/45 (71%)
Procalcitonin (ng/mL) 0.87 ± 1.78 1.53 ± 2.99 0.055
 Increased 63/64 (98%) 62/64 (97%)
Erythrocyte sedimentation rate (mm/H) 41.69 ± 29.25 40.46 ± 30.30 0.704
 Increased 39/58 (67%) 39/58 (67%)
Serum ferritin (ug/L) 1874.52 ± 1974.73 2409.30 ± 2330.41 0.022
 Increased 37/38 (97%) 37/38 (97%)
High sensitive C-reactive protein (mg/L) 112.35 ± 74.51 116.05 ± 84.99 0.703
 Increased 63/70 (90%) 63/70 (90%)

Value listed as mean±SD or N (%).

CT imaging features and dynamic changes

Of 73 patients, 58 patients had only one chest CT scan; 11 had two chest CT scans; three had three chest CT scans; one had four chest CT scans during the disease course (total 93 CT scans). The median time interval between the initial chest CT scans and the last follow-up chest CT scans was five days with a range of 2 to 27 days. The last CT scan was selected to summarize the imaging features for patients with follow-up CT scan(s). Ground-glass opacity with consolidation was the most common feature in each of the five lung lobes (47%-53% among the various lobes; Table 3), followed by GGO in three lobes of the right lung and left upper lobe (16% to 29%), and consolidation in left lower lobe (19%). The most affected lobes were lower lobes of each side of the lung (CT scores of 2.97±1.34 and 2.79±1.34, respectively). The total severity score was 12.97±5.87. The total scores were rated as moderate (11–15 points) and severe (16–20 points) in 22% and 47% patients, respectively.

Table 3. Image characteristics and severity scores of chest CT scans (N = 73).

GGO GGO with Consolidation Consolidation Other CT Score
Right upper lobe 16 (22%) 37 (51%) 12 (16%) 8 (11%) 2.5 1± 1.38
Right middle lobe 21 (29%) 34 (47%) 9 (12%) 9 (12%) 2.32 ± 1.39
Right lower lobe 13 (18%) 39 (53%) 12 (16%) 9 (12%) 2.97 ± 1.34
Left upper lobe 16 (22%) 34 (47%) 11 (15%) 11 (15%) 2.41 ± 1.36
Left lower lobe 12 (16%) 37 (51%) 14 (19%) 10 (14%) 2.79 ± 1.34
Total five lung lobes 12.97 ± 5.87

Value listed as N (%) or mean ± SD.

As compared with the initial chest CT scans, the proportion of GGO with consolidation is markedly increased on the follow-up chest CT scans (Table 4). The averages CT scores were significantly increased on follow-up CT scans than those on initial CT scans for each of the five lobes, as well as the average CT score for both lungs (14.53±5.76 vs. 6.60±5.65; P<0.001). The severity score was rated as severe (white lung) in 13% (2/15) patients based on the initial CT scans, and in 60% (9/15) patients based on the follow-up CT scans (Figs 13).

Table 4. Dynamic changes of imaging features and severity scores between the initial and follow-up CT scans (N = 15).

GGO GGO with Consolidation Consolidation Other CT Score
Initial Follow-up Initial Follow-up Initial Follow-up Initial Follow-up Initial Follow-up P-value
Right upper lobe 2 (13%) 2 (13%) 5 (33%) 12 (80%) 3 (20%) 1 (7%) 5 (33%) 0 (0%) 1.13 ± 1.13 3.07 ± 1.16 <0.001
Right middle lobe 4 (27%) 3 (20%) 4 (27%) 10 (67%) 1 (7%) 1 (7%) 6 (40%) 1 (7%) 1.20 ± 1.21 2.73 ± 1.39 <0.001
Right lower lobe 6 (40%) 1 (7%) 4 (27%) 12 (80%) 1 (7%) 2 (13%) 4 (27%) 0 (0%) 1.53 ± 1.46 3.27 ± 1.16 <0.001
Left upper lobe 5 (33%) 3 (20%) 3 (20%) 10 (67%) 1 (7%) 1 (7%) 6 (40%) 1 (7%) 1.13 ± 1.13 2.53 ± 1.25 <0.001
Left lower lobe 5 (33%) 1 (7%) 6 (40%) 3 (20%) 1 (7%) 9 (60%) 3 (20%) 2 (13%) 1.67 ± 1.23 2.93 ± 1.34 <0.001
Total five lung lobes 6.60 ± 5.65 14.53 ± 5.76 <0.001

Value listed as N (%) or mean ± SD.

Fig 1. Serial chest images of a 57-year-old man with fever and dry cough.

Fig 1

(a-d) 12 days before the death, chest CT with axial, coronal, sagittal planes showed moderate lung involvement with a total CT score of 11, with subpleural ground-glass opacities and patches of consolidation in bilateral lungs. (e-f) 4 days before the death, chest CT with different planes showed severe lung involvement with a total score of 20, with the appearance of the white lung.

Fig 3. Serial chest images of a 59-year-old man with fever, dyspnea, and dry cough.

Fig 3

(a-d) 17 days before death, chest CT with axial, coronal, sagittal planes showed minimal lung involvement with a total CT score of 1, a small piece of ground-glass opacity was found in the right lower lobe. (e-f) 10 days before death, chest CT with different planes showed severe lung involvement with a total score of 19, with an appearance of the white lung.

Fig 2. Serial chest images of a 33-year-old man with fever and dyspnea.

Fig 2

(a-d) 16 days before death, chest CT with axial, coronal, sagittal planes showed moderate lung involvement with a total CT score of 11, appearing as ground-glass opacities (GGOs) with patches of consolidation in bilateral lungs. (e-f) 12 days before death, chest CT with different planes showed severe lung involvement with a total score of 19, appearing as diffusion GGOs with consolidation (white lung).

When tracking back the different periods (<7 days, 7–14 days, >14 days) before the death, the average chest CT scores were 14.93±5.06, 14.09±4.67 and 9.57±6.93, respectively (Table 5). A significant difference was found between the score based on chest CT scans greater than 14 days and those within 14 days before the death (P = 0.004 and 0.013, respectively). The severity scores were rated as severe (white lung) in 57% (17/30), 51% (18/35) and 32% chest CT scans for each period before the death (from near to far).

Table 5. The mean CT scores (mean±sd) the number of patients/CT scans [n (%)] for the different severities of lung involvement between initial chest CT scans and follow-up chest CT scan (N = 15 patients), and among the different periods before the death (N = 93 CT scans).

n Total Score None Minimal Mild Moderate Severe
Initial CT 15 6.60 ± 5.65 1 (7%) 8 (53%) 3 (20%) 1 (7%) 2 (13%)
Follow-up CT 15 14.53 ± 5.76a 0 (0) 2 (13%) 2 (13%) 2 (13%) 9 (60%)
0–7 days 30 14.93 ± 5.06 0 (0) 3 (10%) 3 (10%) 7 (23%) 17 (57%)
7–14 days 35 14.09 ± 4.67 0 (0) 2 (6%) 6 (17%) 9 (26%) 18 (51%)
> 14days 28 9.57 ± 6.93b 1 (4%) 11 (39%) 4 (14%) 3 (11%) 9 (32%)

a. significant difference between initial and follow-up chest CT scans by Wilcoxon signed-rank test;

b. significant difference between the group with 14 days more and the groups with 0–7 and 7–14 days before the death by Mann-Whitney U test.

Correlation of CT scores and inflammatory parameters

Moderate positive correlations were found between mean CT scores and leucocytes (r = 0.581, P<0.001), neutrophils (r = 0.587, P<0.001), and IL-2R (r = 0.447, P = 0.003). Week positive correlations were found between mean CT scores and neutrophil-to-lymphocyte ratio (r = 0.300, P = 0.012), and IL-8 (r = 0.332, P = 0.030). A week negative correlation was found between mean CT scores and lymphocytes (r = -0.286, P = 0.019; Fig 4).

Fig 4. The correlations of CT scores and inflammation-related parameters.

Fig 4

Discussion

With the rapid spread of COVID-19 around the world, it has stirred up an international concern. This study preliminarily demonstrated the features of chest CT imaging in severe patients died from COVID-19. By lung lobe-based analysis, the typical imaging features of GGO with consolidation was found in 47%-53% patients died from COVID-19, with an average severity score of 12.97±5.87. The proportions of consolidation and severity scores were significantly increased with the disease progression; meanwhile, the white lung was observed in more than half of the patients as early as 7–14 days before the death. In addition, moderate correlations between the severity of pulmonary inflammation based on chest CT imaging and inflammatory parameters (leukocytes, neutrophils, and IL-2R) were also firstly found in this study.

In this study, the average age of the patients was 67±12 years old; most of them had at least one underlying disease such as hypertension, diabetes, cardiovascular or cerebrovascular diseases. This is agreed with the previous report that the older patient with COVID-19 tends to become more severe, in particular for the patients with underlying diseases [10]. Fever and dry cough were the main symptoms after the onset of SARS-CoV-2 infection, which is similar to the symptoms of SARS or MERS [11]. For the laboratory, the significant increase in leukocytes, neutrophils and neutrophil-to-lymphocyte ratio suggested the severity of pulmonary inflammatory responses and impairment of the immune system in patients infected with SARS-CoV-2 [12]. The infection-related biomarkers including SF markedly elevated in the serum as well as Inflammatory cytokines including IL-6, and TNF-α, indicating that inflammation storm may also occur and aggravate in patients died from COVID-19 during the disease [1317].

Chest CT imaging plays an important role in the diagnosis and dynamic evaluation of COVID-19. Typical imaging features of multiple ground-glass opacities and/or consolidations in patients with COVID-19 pneumonia have been detailedly described in previous reports [18, 19]. Even though the pathogenesis of SARS-CoV-2 infection is not fully understood, diffuse alveolar injury and progressive respiratory failure caused by SARS-CoV-2 is the leading cause of death in severe patients with COVID-19 [20]. From the current study, we found GGO and GGO with consolidation were the most predominant imaging features in patients who died from COVID-19, which is correlated with the pathological findings of COVID-19 that severe inflammatory exudation in intra-alveolar spaces and hyaline membrane formation [20, 21]. The severity score of lung involvement in patients who died from COVID-19 was also significantly greater than that in patients with mild to moderate COVID-19 (12.97±5.87 vs. 7±4) [6]. What is more, the mild-moderate correlation between chest CT severity scores and systemic inflammation activation was also preliminarily demonstrated in this study. Therefore, the imaging features and dynamic changes could provide the most direct evidence for assessing the severity of the disease and the prognosis.

The results of this study also demonstrated that the proportions of consolidation and severity scores were significantly increased on the follow-up chest CT scans as compared with the initial CT scans (14.53 ± 5.76 vs. 6.60 ± 5.65) in patients died from COVID-19. More white lungs (severe lung involvement) were observed in the late stage of the disease (57% vs. 32% for 0–7 days and >14 days before the death). In addition, considering the correlations between chest CT scores (lung involvement) and inflammatory parameters of laboratory tests, the increase of the proportions of consolidation and the extent of GGO (higher CT scores) would suggest secondary bacterial infection occurred in the late stage of SARS-CoV-2 infection, which may be responsible for the rapid deterioration and acute respiratory distress in severe patients with COVID-19. Empirically administration of antibacterial drugs was thus recommended by some clinical experts. Therefore, rapidly increased consolidation and high severity scores based on chest CT images may predict the patient’s poor prognosis.

The outbreak of COVID-19 has had a strong impact worldwide. Almost all countries have suffered huge losses in health, society and economy [22]. Our results may be potential risk factors to identify patients with poor prognosis, help clinicians to provide earlier interventions for these patients, and improve their survival rate.

There were some limitations in this present study. First, there was no control group included in this study. Thus, it is hard to evaluate the exact value of chest CT imaging in identifying the risk factors of poor prognosis as compared with the other clinical and/or laboratory parameters. A case-control study needs to be done shortly. Second, because many patients were transferred from the other hospitals, their early chest CT images were not available for us. In addition, some patients did not have follow-up chest CT scans due to critically ill conditions. As lung biopsy was lacked, the relationship between imaging features and histopathological findings needs to be investigated. Therefore, other potential causes of underlying disease were not estimated. Therefore, the information of dynamic changes of CT features and severity scores is limited.

Conclusion

Chest CT findings and laboratory test results were worsening in patients who died of COVID-19, with moderate positive correlations between CT severity scores and inflammation-related factors of leucocytes, neutrophils, and IL-2R demonstrated in this study. Our results and analysis suggest that chest CT features and severity scores with dynamic changes may serve as potential risk factors helping clinicians to identify patients with poor prognosis.

Acknowledgments

Thanks W.Z.L. for the contribution to data collection.

Data Availability

All relevant data are within the manuscript.

Funding Statement

The author(s) received no specific funding for this work.

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Decision Letter 0

Muhammad Adrish

7 Jul 2020

PONE-D-20-16666

Chest CT Findings Related to Mortality of Patients with COVID-19: A Retrospective Case-series Study

PLOS ONE

Dear Dr. Tao Ai,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

I have received the comments of the reviewers on your manuscript. The specific comments of the reviewers are included below. Please provide point by point response in your revised manuscript.

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We look forward to receiving your revised manuscript.

Kind regards,

Muhammad Adrish

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I read with interest the mansuscript. I find it well wrote.

Only some suggestions:

1. Introduction: -include data on COVID 19 global burden at the time of the revision

2. Methods: clear

3. Results: I appreciate a lot the results, the table and the figure. Well done!

4. Discussion: discuss about the future perspective from your data and cite this article ( Coronavirus Diseases (COVID-19) Current Status and Future Perspectives: A Narrative Review. Int J Environ Res Public Health. 2020;17(8):2690. Published 2020 Apr 14.)

Reviewer #2: The manuscript entitled:"Chest CT Findings Related to Mortality of Patients with COVID-19: A Retrospective Case-series Study" is a retrospective study about the correllation between chest CT scan features, inflammatory serological markers and mortality rate in COVID-19 patients.

The questions are:

1) The Author reports an increase in neutrophyl/limphocites ratio near the death but does not specify the number of patients who had bacterial infection, can clarify please?

2) The Author reports the severity score of chest CT scan, can clarify the meaning of " severity score"?

3) What are the clinical signs of disease worsening as intended by the Author?

4) Why did the Author chose to measure the receptor of IL-2 as inflammatory marker?

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Francesco Di Gennaro

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

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PLoS One. 2020 Aug 25;15(8):e0237302. doi: 10.1371/journal.pone.0237302.r002

Author response to Decision Letter 0


23 Jul 2020

Dear Dr. Muhammad Adrish (Academic Editor)

We appreciate the timely and thoughtful comments from you and the reviewers on our manuscript (PONE-D-20-16666) entitled "Chest CT Findings Related to Mortality of Patients with COVID-19: A Retrospective Case-series Study”. We thoroughly reviewed all comments and have carefully revised our manuscript accordingly.

Attached is our revised manuscript and detailed responses to the comments point by point. We hope that you will find our changes satisfactory.

Again, thank you very much and we look forward to hearing from you soon!

Sincerely,

TAO AI

====================================================================

Journal Requirements:

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Response: : Truly thank you for the comment. We have modified the article to meet PLOS ONE’s style requirements.

2.Please correct your reference to "p=0.000" to "p<0.001" or as similarly appropriate, as p values cannot equal zero.

Response: : Thank you for the comment. We have modified the P value in the article.

3.Thank you for stating the following in the Financial Disclosure section:

'The author(s) received no specific funding for this work.'

We note that one or more of the authors are employed by a commercial company: Julei Technology Company

Response: : Thank you for the comment. We decided to delete the author from our article, and thanks his contribution in Acknowledgement.

-----------------------------------------------------------------

Comments to the Author:

Reviewer #1

Introduction: -include data on COVID 19 global burden at the time of the revision

Response: : Truly thank you for the comment. The related information has been updated.

Methods: clear

Response: Thanks for your comment.

Results: I appreciate a lot the results, the table and the figure. Well done!

Response: Thanks for your comment.

Discussion: discuss about the future perspective from your data and cite this article ( Coronavirus Diseases (COVID-19) Current Status and Future Perspectives: A Narrative Review. Int J Environ Res Public Health. 2020;17(8):2690. Published 2020 Apr 14.)

Response: Thanks for your comment. We discussed about the future perspective from your data and added the literature according your suggestion.

-----------------------------------------------------------------

Reviewer #2

The Author reports an increase in neutrophyl/lymphocites ratio near the death but does not specify the number of patients who had bacterial infection, can clarify please?

Response: Thanks for your concern. Yes,elevated Neutrophils, high sensitive CRP and decreased Lymphocytes were very common in patients with severe COVID-19, suggesting that second pulmonary bacterial infection plays an important role in the progression of the diseases (which may correlated with rapidly progressing lung consolidation/white lung). However, pathogen identification such as bacteria culture to confirm the infection of bacteria had been performed during the early time of the outbreak because of the long-time consumption of bacteria culture and potential risks when obtaining sputum specimens. Thus, in Chinese practice, early empirical treatment with antibiotics covering common pathogens was strongly suggested to be administered after analyzing clinical symptoms, and marked elevated levels of neutrophils and hs-CRP in serum, to prevent the occurrence of septic sepsis/multi-organ dysfunction .

The Author reports the severity score of chest CT scan, can clarify the meaning of " severity score"?

Response: Thanks for your comment. Severity score of chest CT means the range of lesions involvement. The higher the score, the wider the range of lesion involvement. The relevant content was mentioned in article, which appears in Materials and methods section CT image analysis: “Each of the five lung lobes was visually scored for the degree of lung involvements using a 4-point- scale: 0, no involvement; 1, 1-25% involvement; 2, 26%-49% involvement; 3, 50%-75% involvement; 4, 76%-100% involvement. The total severity CT score (the extent of pulmonary disease) was the sum of the five individual lobar scores and defined as follows: 0, none; 1-5, minimal; 6-10, mild; 11-15, moderate; and 16-20, severe involvement of the lung (white lung).” The method of severity score evaluated chest CT was from Bernheim [1].

[1] Bernheim A, Mei X, Huang M, et al. Chest CT Findings in Coronavirus Disease-19 (COVID-19): Relationship to Duration of Infection. Radiology. 2020;295(3):200463.

What are the clinical signs of disease worsening as intended by the Author?

Response: Thanks for your comment. In clinical aspect, the signs of disease worsening refers dyspnea that cannot be improved, irreversibly decreased blood oxygen saturation, decreased lymphocytes and increased level of inflammatory factors. In radiology aspect, the clinical signs of disease worsening are increased proportions of consolidation and increased chest CT severity scores.

Why did the Author choose to measure the receptor of IL-2 as inflammatory marker?

Response: Thanks for your comment. IL-2R, similar to TNF-α, IL-1β, IL-6 and IL-8, is a kind of inflammatory cytokines, which is a necessary signal for immune response. Meanwhile, pervious studies have demonstrated that the concentration of IL-2R was significantly changed in COVID-19 patients [2,3]. Therefore, we chose IL-2R.

[2] Chen G, Wu D, Guo W, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020;130(5):2620-2629.

[3] Hou H, Zhang B, Huang H, et al. Using IL-2R/lymphocytes for predicting the clinical progression of patients with COVID-19. Clin Exp Immunol. 2020;201(1):76-84.

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 1

Muhammad Adrish

27 Jul 2020

Chest CT Findings Related to Mortality of Patients with COVID-19 : A Retrospective Case-series Study

PONE-D-20-16666R1

Dear Dr. Tao Ai,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Muhammad Adrish

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I appreciate a lot your paper

Authors improve their manuscript following reviewer suggestions

I think that is a good example of good interaction beetwen editor authors and reviewer

Congratulations

Reviewer #2: The Author replied satisfactorily to all questions and in my opinion the paper can be published in PlosOne journal

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Francesco Di Gennaro

Reviewer #2: No

Acceptance letter

Muhammad Adrish

17 Aug 2020

PONE-D-20-16666R1

Chest CT Findings Related to Mortality of Patients with COVID-19: A Retrospective Case-series Study

Dear Dr. Ai:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Muhammad Adrish

Academic Editor

PLOS ONE

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    Supplementary Materials

    Attachment

    Submitted filename: Response to Reviewers.docx

    Data Availability Statement

    All relevant data are within the manuscript.


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